Gender differences in neurological disease: role of estrogens and cytokines

Increasing evidence suggests that inflammatory response may be a critical component of different brain pathologies. However, the role played by this reaction is not fully understood. The present findings suggest that neuroinflammtory mediators such as cytokines may be involved in a number of key steps in the pathological cascade of events leading to neuronal injury. This hypothesis is strongly supported by experimental and clinical observations indicating that inhibition of the inflammatory reaction correlates with less neuronal damage. Estrogens are thought to play a role in the sex difference observed in many neurological diseases with inflammatory components including stroke, Alzheimer's and Parkinson's diseases, multiple sclerosis, or amyotrophic lateral sclerosis. Clinical and experimental studies have established estrogen as a neuroprotective hormone in these diseases. However, the exact mechanisms involved in the neuroprotective effects of estrogens are still unclear. It is possible that the beneficial effects of these hormones may be dependent on their inhibitory activity on the inflammatory reaction associated with the above-mentioned brain pathologies. Here, we review the current clinical and experimental evidence with respect to the inflammation-modulating effects of estrogens as one potential explanatory factor for sexual dimorzphism in the prevalence of numerous neurological diseases.